Abstract 1355: Evolution of immune tumor microenvironment (TME) from esophageal dysplasia to esophageal squamous cell carcinoma (ESCC)
Authors: Jhe-Cyuan Guo, Chia-Lang Hsu, Yen-Lin Huang, Tsung-Che Wu, Chih-Hung Hsu
Journal: Cancer Research (2023)

Abstract Background: Previous studies have revealed esophageal dysplasia, a precancerous lesion of ESCC, harbors similar mutations and markers of genomic instability as ESCC does. This observation suggests that other factors such as evasion of immune surveillance may be involved in the progression of esophageal dysplasia to ESCC. The study aimed to identify the key differences in the immune TME between esophageal dysplasia and ESCC. Methods: Patients with a history of diagnosing with esophageal dysplasia for at least two times prior to the diagnosis of ESCC were enrolled. Formalin-fixed paraffin-embedded tissues from esophageal dysplasia diagnosed more than 6 months prior to the diagnosis of ESCC (denoted as dysplasia-1), esophageal dysplasia diagnosed within 6 months prior to the diagnosis of ESCC (denoted as dysplasia-2), and ESCC were retrieved. Transcriptomic data of esophageal dysplasia and ESCC tissues were generated by NanoString nCounter platform with Human PanCancer Immune Profiling panel, and were further analyzed for the expression levels of infiltrating immune cells by CIBERSORT. Results Six ESCC patients (M:F= 6:0), with median age of 56.6 (range: 43.3-79.1) years, were enrolled. The median time between the diagnosis of dysplasia-1 and that of ESCC was 10.2 months (range 6.0-38.6) and the median time between the diagnosis of dysplasia-2 and that of ESCC was 2.3 months (range 0.0-6.0). The analysis of immune cell signatures defined by NanoString platform revealed that multiple cell types were significantly increased in ESCC compared with dysplasia-1 (mast cell, macrophage, CD8 T cell, B cell and dendritic cell, all P &amp;lt; 0.05) and in ESCC compared with dysplasia-2 (macrophage, mast cell, dendritic cell, B cell, T cell, CD4 T cell, regulatory T cell, cytotoxic T cell, NK CD56dim cell, and T helper cell, all P &amp;lt; 0.05). There was no significant difference in the immune cell signatures between dysplasia-1 and dysplasia-2. Immune cells classified by CIBERSORT showed an increase of M2 macrophage and a decrease of M1/M2 ratio in ESCC compared with dysplasia-1 or dysplasia-2 (both P &amp;lt; 0.05). Conclusions: Our data, showing an increase of M2 macrophage in TME of ESCC compared with its precancerous esophageal dysplasia, suggest that evolution of immune TME may play a role in the progression of esophageal dysplasia to ESCC. (Funded by MOST 108-2314-B-002-076-MY3, MOST 109-2314-B-002-231-, MOHW 111-TDU-B-221-114006, NTUCCS-110-10, and NTUCCS-111-05) Citation Format: Jhe-Cyuan Guo, Chia-Lang Hsu, Yen-Lin Huang, Tsung-Che Wu, Chih-Hung Hsu. Evolution of immune tumor microenvironment (TME) from esophageal dysplasia to esophageal squamous cell carcinoma (ESCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1355.